(1325-B) Insights into the Molecular Mode of Action of Compounds Targeting Nucleases and Helicases Utilizing switchSENSE
Monday, February 5, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: Helicases and nucleases are significant targets in drug discovery. The identification of inhibitors in these target classes is often achieved through high-throughput screenings utilizing biochemical assays. We have successfully conducted multiple hit-finding campaigns using a screening deck containing over 1 million small molecules. To elucidate the molecular mode of action of the identified hits, various assays are employed in early drug discovery projects. Over the past two years, we have discovered that switchSENSE technology plays a crucial role in these cascades for hit prioritization. One application involves assessing the binding behavior of molecules to oligonucleotides (substrates of the target enzyme) to exclude non-specific pharmacologies identified in biochemical screening campaigns. Another application involves evaluating the catalytic activity of the target enzyme using switchSENSE. By leveraging the flexibility of oligonucleotide design and the enhanced sensitivity and throughput of the latest generation of switchSENSE devices, we have established assays across different projects to gain insights into the molecular mode of action of compounds targeting helicases and nucleases. In conclusion, the integration of switchSENSE in helicase and nuclease drug discovery projects has facilitated the prioritization and comprehension of small molecules, leading to faster decision-making and resource savings.